Effects of sevoflurane postconditioning on oncosis and apoptosis in cardiomyocytes during ischemia-reperfusion in isolated rat hearts: relationship with ERK1/2 signal transduction pathway

Objective To evaluate the effects of sevoflurane postconditioning on the oncosis and apoptosis in cardiomyocytes during ischemia-reperfusion (I/R) in isolated rat hearts and the role of extracellular signalregulated protein kinase 1/2 (ERK1/2) signal transduction pathway in it.Methods Seventy-two isolated rat hearts perfused in a Langendorff apparatus were randomly divided into 6 groups (n =12 each) using a random number table:sham operation group (group S),myocardial I/R group (group I/R),sevoflurane postconditioning group (group SP),PD98059 vehicle dimethyl sulfoxide (DMSO) group (group DMSO),selective ERK1/2 inhibitor PD98059 group (group PD),and sevoflurane postconditioning + PD98059 group (group SP + PD).The hearts were subjected to ischemia for 30 min followed by 2 h reperfusion in the other groups except group S.In SP,DMSO and PD groups,the hearts were perfused with K-H solution saturated with 3.0％ sevoflurane,DMSO (＜0.2％) and PD98059 (20 μmol/L),respectively,for 15 min starting from the end of ischemia until 15 min of reperfusion,and then with plain K-H solution for 105 min.In group SP+ PD,the hearts were perfused with K-H solution saturated with 3.0％ sevoflurane and PD98059 for 15 min starting from the end of ischemia until 15 min of reperfusion.Myocardial infarct size and expression of porimin and caspase-8 proteins (by Western blot) were measured at the end of reperfusion.Results Compared with S group,the myocardial infarct size was significantly increased,and the expression of porimin and caspase-8 proteins was up-regulated in the other groups (P ＜ 0.05).Compared with I/R group,the myocardial infarct size was significantly decreased,and the expression of porimin and caspase-8 proteins was down-regulated in group SP (P ＜ 0.05),and no significant changes were found in the other groups (P ＞ 0.05).Conclusion Sevoflurane postconditioning can activate ERK1/2 signal transduction pathway and inhibit the oncosis and apoptosis in cardiomyocytes,thus attenuating I/R injury in isolated rat hearts. Key words: Anesthetics, inhalation;  Myocardial reperfusion injury;  Cell death;  Extracellular signal-regulated MAP kinases